Theoretical and Translational Medicine 2.
Kovács, Domonkos Előd
Semmelweis University, Department of Internal Medicine and Oncology; Department of Physiology
Domonkos Előd Kovács1,3, Márk Juha1, Adél Molnár1, Gergely Péter Máté1, Petra Anna Kurucz1, Magdolna Kardos2, Deján Dobi2, Zoltán Jakus3, Nóra Ledó1,3
1: Semmelweis University, Department of Internal Medicine and Oncology
2: Semmelweis University, Department of Pathology, Forensic and Insurance Medicine
3: Semmelweis University, Department of Physiology
Introduction: Lupus nephritis (LN) occurs in half of the patients with systemic lupus erythematosus. The accumulation of autoantibodies against nuclear and cellular components leads to immune complex formation and tissue damage. The endonuclease enzymes, including deoxyribonuclease 1 (DNase1), may help clear the nuclear debris, but their exact role in LN is still unknown.
Aims: The aim of this study is to define the expression pattern of DNase1 and correlate to disease activity in LN.
Methods: We examined renal specimens and clinical data of patients who underwent kidney biopsy in our centre between 2005 and 2020. DNase1 expression was assessed by immunofluorescence in paraffin-embedded samples. ImageJ and SPSS Statistics software were used to determine the immunofluorescent intensity and analyse the data, respectively.
Results: From the 91 kidney biopsies, DNase1 staining was performed on 82 samples based on availability, and 71 were analysed after quality control. Median age was 36 (min. 18, max. 74) years, 86% were female. Laboratory measurements were available in 68 cases. Median creatinine was 85.5 (min. 35, max. 525) µmol/L. Glomerular intensity of DNase1 showed positive correlation with serum creatinine (rs=0.311; p=0.007), urea (rs=0.249; p=0.041), potassium (rs=0.285; p=0.018), and time to remission (rs=0.353; p=0.018); while a negative correlation with eGFR (rs= -0.295; p=0.015) was observed. Tubular DNase1 intensity showed correlation solely with glomerular intensity.
Conclusion: Glomerular DNase1 expression correlates with the severity of LN and the response to treatment. We theorize that elevated DNase1 expression may serve as a compensatory response to glomerular damage caused by immunocomplexes. Glomerular DNase1 intensity may serve as a potential marker of disease progression.
Funding: Nóra Ledó was supported by the National Research, Development and Innovation Office, Hungary. Grant number: FK_142911. Zoltán Jakus was supported by TKP2021-EGA-29 and TKP2021-EGA-24.